XMRV CFS UK study #II

[Gerwyn]

I was reading an article Kurt recommended about the search for retroviruses in various illnesses. (See my HERV and XMRV thread in this subforum.)

The odd thing about this study is that Kurt's article talks about how people with various autoimmune/ inflammatory conditions commonly produce antibodies to a retroviral/ HERV fragments leading to false-positive antibody results. I think CFS, whatever the cause, is a chronic inflammatory state (supported by some prior studies). If so, the odd thing is the ABSENCE of antibodies in the whole CFS group (except one person) in this study. I would expect more CFS subjects to have antibodies, even false-positive antibodies. Or, as discussed earlier, if by entirely random chance, the same percentage of antibodies as the controls.

Which leads me to think about the one sentence the researchers give about CFS subjects unable to produce antibodies due to poor immune status. Here's a truly wild thought............they did mention a very small number of controls having neutralizing antibodies specific for XMRV. What if they could characterize that antibody more and produce it as vaccine therapy for CFS sufferers? I'm skipping a whole bunch of steps here but this makes me wonder.........................

I recently posted my concerns re the abnormally high levels of endogenous retroviruses in the control group due to the various ilnesses they suffered from---these are all associated with high levels of endo proteins--I could not understand however why they included pregnant women as well but------

Endogenous retoviruses are involved in placental differentiation and immunosuppression during pregnancy So the entire control group had massively greater expression of endogenous retroviuses than the normal population.The chance of any PCR test not producing positive results in this control group would be microscopically small!

 

[Revday]

Thank you Donna.

 

[usedtobeperkytina]

Well, I wonder, (actually I am pretty sure I know), whether the Uk study researchers will read the WPI statement.

Tina

 

[Bob]

Neither UK study requested positive control blood, plasma or nucleic acids from the WPI

Does anybody on the forum have any insight into why the WPI and Jonathan Kerr did not collaborate on the UK research in any way whatsoever?
I mean, Kerr and Mikovtis are on good speaking terms, and they are partners, so why did we have this breakdown in communication and collaboration?

 

[Bob]

Hi everyone,
I'm posting this because I hope it will be a bit of encouragement for everyone...
it's a proposed research study to be undertaken by Jonathan Kerr, if he gets the funding... here's a link with the details:
http://www.investinme.org/IIME Biomedical Research 2009 12 01 Kerr.htm

He wants to use his gene expression work and the XMRV virus together, and correlate gene expression with XMRV...
"XMRV status will be related to ME/CFS gene expression changes"
All this work is still in it's infancy, so we'll have to be patient...
but there are some really serious studies being carried out, like this one, which i find really encouraging.

(Admin - if this would be better posted somewhere else, then please do.)

 

[kurt]

Does anybody on the forum have any insight into why the WPI and Jonathan Kerr did not collaborate on the UK research in any way whatsoever?
I mean, Kerr and Mikovtis are on good speaking terms, and they are partners, so why did we have this breakdown in communication and collaboration?

This is just a wild guess, but right now there is no accepted commercial PCR test for XMRV. So it is a bit of a race. A definition - replication is to prove that a test works, validation is to prove that the test's finding is accurate. If a lab has the goal of replication only they will use the identical measures of WPI. If the lab has the goal of validation or commercialization of their own test, they will build their own testing and acquire their own samples. This is stronger science and allows them eventual patent rights.

If a validation study were to find XMRV they would then have a viable commercial testing product to license. Researchers may often work in non-profits but their labs require funding just like any group, and the idea of a stream of royalty income to fund ongoing research is very appealing to them. Note that is how WPI set things up with VIP Dx, this is a common strategy nowadays.

So it does not matter if you are friends with the original lab in a case like this, you still are competing, just like teammates competing in individual sports in the Olympics, you want your teammates to also win a medal, but you still are also competing against your friends for the gold (they can have silver).

Also, there is nothing wrong with the Kerr or IC approach to XMRV testing, they were both gambling and lost that bet. But if they had found XMRV by a different method/approach, that would have been a powerful find, that would have validated that XMRV is found in CFS. That would also have possibly given them a test of their own to market (which IC has done already for research purposes). And that was apparently a worthwhile gamble for them, and probably will be for other labs yet to announce findings. There is no real financial incentive to replicate precisely, except maybe for the CDC or DHHS who have different funding and a different mandate.

The idea that everyone should just be trying to replicate the WPI finding precisely, something I am certain WPI would like, actually works against the commercial and even non-profit interests of the other labs.

Science is still operating in a Capitalistic environment here, people will compete as hard as in any other field, the fact that we are underserved just makes our market more interesting. But they will cooperate, if someone pays them to, or when there is no other option left and they are forced to work together. Just as in any other competitive field.

 

[flex]

Does anybody on the forum have any insight into why the WPI and Jonathan Kerr did not collaborate on the UK research in any way whatsoever?
I mean, Kerr and Mikovtis are on good speaking terms, and they are partners, so why did we have this breakdown in communication and collaboration?

It was the MRC that was in control of this study. An organisation that for decades has refused one single penny for bio medical testing to any research group. The MRC is supposedly independent from government, but effectively it is state run. The MRC have been the figureheads for allowing the psyche lobby to run and control ME in this country for decades. Just like the CDC in the states.

This is the kind of state sponsored result the MRC wanted and they made damn sure they got it. Just because Kerrs name was on this study doesn't mean he had any control, power or say in it. For all we know he was told to put his name to it or else:

1) No more studies for you.
2) You will miss out on the chance to be at the forefront of a major scientific breakthrough. (NOT!!)


The aim of the UK government is to go one for one with every study that finds XMRV and produce or quote another, probably European, study that finds negative results. This will allow them to claim, "the science is unsettled". Just like people are trying to say with the climate change debate.

Then they will get to a stage where they can do a "study of studies" and claim there is no overriding evidence of XMRV in ME. There aim is to break down the whole process before a casual link can be proven. The next step will be for them to deny any further research be done on the basis of anything other than evidence supplied by the government. Their bias information will be rolled out to the mainstream of the medical profession who are to busy or naive to follow this debate. It will then form policy.This is exactly the process they followed with MMR and GWS, Malcolm Hooper has often stated this.

So I guess the answer to Bobs question is: Kerr is dangerous to the establishment. Who has more power, one doctor Kerr or the whole of the British establishment. What would have happened if Kerr had said, "sorry I dont want to be part of your study"?

Will they get away with it this time. They have no choice but to try. There are years and years of incompetence to cover up here. Not to mention hundreds if not thousands of reputations.

Time will tell if crime pays!!

Let us not forget - Crime wont crack itself!!

 

[Gerwyn]

This is just a wild guess, but right now there is no accepted commercial PCR test for XMRV. So it is a bit of a race. A definition - replication is to prove that a test works, validation is to prove that the test's finding is accurate. If a lab has the goal of replication only they will use the identical measures of WPI. If the lab has the goal of validation or commercialization of their own test, they will build their own testing and acquire their own samples. This is stronger science and allows them eventual patent rights.

If a validation study were to find XMRV they would then have a viable commercial testing product to license. Researchers may often work in non-profits but their labs require funding just like any group, and the idea of a stream of royalty income to fund ongoing research is very appealing to them. Note that is how WPI set things up with VIP Dx, this is a common strategy nowadays.

So it does not matter if you are friends with the original lab in a case like this, you still are competing, just like teammates competing in individual sports in the Olympics, you want your teammates to also win a medal, but you still are also competing against your friends for the gold (they can have silver).

Also, there is nothing wrong with the Kerr or IC approach to XMRV testing, they were both gambling and lost that bet. But if they had found XMRV by a different method/approach, that would have been a powerful find, that would have validated that XMRV is found in CFS. That would also have possibly given them a test of their own to market (which IC has done already for research purposes). And that was apparently a worthwhile gamble for them, and probably will be for other labs yet to announce findings. There is no real financial incentive to replicate precisely, except maybe for the CDC or DHHS who have different funding and a different mandate.

The idea that everyone should just be trying to replicate the WPI finding precisely, something I am certain WPI would like, actually works against the commercial and even non-profit interests of the other labs.

Science is still operating in a Capitalistic environment here, people will compete as hard as in any other field, the fact that we are underserved just makes our market more interesting. But they will cooperate, if someone pays them to, or when there is no other option left and they are forced to work together. Just as in any other competitive field.

you must replicate in order to validate in other words if yiu have an unproven test you must first calibrate your test against one that is known to work and you must apply that test first in exactly the same conditions as the first test first then try and see if your test works in other conditions you must also use the first test and you must use healthy controls.lNone of this ws done so the approach was unscientific -there were far too many variables and science is not about guessing or assuming when there is evidence to the contrary

 

[Gerwyn]

(
Parsimony is a principle in science wich is used to guide the production of a hypothesis .It entails providing the simplest or most frugal explanation to account for phenomena.in simple terms the least complex(one with the fewest components) explanation is preferred.a commonly referred label is Occams razor.this avoids something called overfilling where a theory loses its predictive power.it is really a rule of thumb(heuristic) heavily relied on by Einstein in particular and the development of quantum theory in particular.

The most parsimonious explanation for the results in the new british study is that the assay method was not sensitive enough to detect XMRV and could only detect viruses in the control group because the levels of retroviral expression were many times the normal value

 

[garcia]

Great post Kurt.

We don't know how much input Jonathan Kerr had on the methodology vis-a-vis Bishop and Stoye. Given the last 2 are retrovirologists, I'm guessing they would have had final say on the methodology used. Also when they started this work, they didn't know all the things we know now (about the difficulty of detection, that PCR isn't so accurate etc.). Being retrovirologists they probably treated XMRV like it was HIV/HTLV in terms of detection. Only we know it's not that easy.

 

[bullybeef]

Someone on another forum pointed out the following:

"JK, JS and KB conceived and designed the investigation.
HG and VB carried out the viral neutralisation assays and analysed the data.
KM, ER, SB and JK performed the PCR analyses.
SH, JG, FM, JB and JK provided patient samples.
JS and KB analysed the data and drafted the manuscript.
All authors read and approved the final manuscript."

It clearly states JK was one of three whom actually performed the PCR analysis and provided the patient samples. I still have yet to understand why Dr. Kerr would perform this procedure if he was privy to Dr. Mikovits specific PCR mythology based upon his publicised collaboration.

 

[Bob]

Kurt and flex, thanks very much for your full explanations...
I can see that individual scientists' egos and careers were at work here,
along with funding issues... and MRC politics...
and the compromises that you inevitably get with collaborative work.

Like flex says, this was a publicly funded research study, as the MRC is a public body,
and so we can't ignore the long-standing politics of the MRC.

I think that Jonathan Kerr must have been constrained here to work in collaboration with the others.
I think he works best when he has the freedom of working alone, and doesn't have to compromise.
(i don't know much about the other researchers)

The funding coming from the MRC for ME is tiny, baring in mind that it's the UK's main research funding body... it was a total of 728,000 in 2008/2009 ($1,121,000) (the cost of a medium sized house in London), and none of it went towards biomedical research - only psycho-social research (CBT etc)...
Jonathan Kerr says that all of his grant applications were turned down... they were blocked by psychiatrists on the MRC's grant referee panel...
his applications typically received a score of 9,8,3... and the 3's, which effectively blocked his grant applications, were given by psychiatrists who didn't agree with his patient selection criteria (i.e. they wanted chronic fatigue patients, not ME patients).

The MRC says that it is working towards a better understanding of ME, and the new(ish) head of the MRC recently acknowledged that ME wasn't all in the mind, but that there were 'real' physiological cellular processes at work...
so maybe things are moving forwards... i hope that this latest research study will be a turning point for the MRC and that they will soon have to acknowledge that research into ME needs more specific diagnostic criteria...

I still have loads of faith in Jonathan Kerr.

 

[flex]

Hi Bob,

I too have faith in Jonathan Kerr. I think he may just have played "their" game a little so that he could play his own when he does his own study in collaboration with the WPI. Hopefully just keeping his enemies close and keeping them sweet. Maybe Kerr thought "If I don't take part in this study who will they put in my place and how much worse could it be". At least he was able to talk from the inside about the flaws in this study.

 

[George]

Flex

Has Dr. Kerr made any statement about the study?

 

[flex]

Has Dr. Kerr made any statement about the study?

George, I am not sure who exactly said it but it went along the lines. "we still need to collaborate and define a consistent method that will give us an insight into this neurological disease". I'll have a look when I get the chance.

 

[Esther12]

Has Dr. Kerr made any statement about the study?

I think this is important.

We shouldn't start writing stories about how Kerr had to put his name on a study not finding XMRV just to make his future study finding XMRV more credible, etc, etc. As far as I'm aware, we've got nothing credible to support these sorts of claims. I know we all want to have something which can kick-start CFS research, but it's still quite possible the XMRV link won't hold up, and these negative studies will turn out to be right, while it's the WPI's that is flawed/

 

[George]

Please do Flex

That could be a really important statement!

 

[Cort]

I can't imagine Kerr would not have signed onto a study he didn't have faith in. (Klimas talked about finding the right collaborators). That group expected to find XMRV. I'm sure they thought this study - with a world renowned virologist on board as Dr. Vernon pointed out and several ME/CFS researchers - would validate the WPI's results. A successful validation study appears to be better than a successful replication study - since as Kurt pointed out - it employs different techniques to still find the bug - which really solidifies the original result - so while monetary interests may be involved (when are they not!) they must have also thought they were doing the WPI a favor.

Only time will tell if they missed something - the culturing for instance - but it was obviously a good faith effort. As primitive as this bug is it appears to be turning out to be more complicated than expected (unfortunately). Thankfully this time there appears to be enough interest for the research world to buckle down and figure out what's going on.

 

[billyd242]

Leaving aside the motivations of a research team, it seems irresponsible to not FIRST try and replicate the findings. There is plenty of time for validation studies, but the first thing that should have happened is somone trying to replicate the study to see if they got similar results.

One of the first things you learn is science class as a kid about scientific experiments is to control as much as possible. It's a no brainer that the very first thing that should have been done is to see if someone else can get similar results using the same protocols.

I can't believe we are still waiting for someone to make this simple step forward in this research.

We can debate all day which protocols are better and the value of validation studies and the significance of other testing methods not detecting XMRV in PWCs, but my gosh, can someone please do the only logical next step in this research and try and replicate the WPIs finding using THEIR protocols and some of their samples?

 

[Hysterical Woman]

Hi billyd,

We understand your frustrations!!!

Welcome to the forums,

Hysterical